A new kind of cancer treatment works remarkably well for some patients but not others -- and researchers want to know why

For some cancer patients, a new group of drugs has led to remarkable remissions with few side effects. But others have tried them, only to find little benefit and a lot of discomfort.

The treatment, broadly speaking, is called cancer immunotherapy. These drugs — many of which have become available in the past few years — have led to cautious optimism among oncologists who often had few options for treating certain cancers. Cancer researchers see promise. Drug companies see potential for a new group of mega moneymakers. Investors and billionaires, like former New York Mayor Michael Bloomberg and Silicon Valley billionaire Sean Parker, have invested hundreds of millions into researching new treatments.

Yet it’s still early days, and there’s as much hope as confusion over the new treatments true potential and possible risks.

The promise

In August 2015, former US President Jimmy Carter, then 91, announced he had cancer. The diagnosis was metastatic melanoma, and it had spread to his brain. He thought he had merely weeks to live.

That remarkable turn came from a combination of a traditional therapy, radiation, and a new one, an immunotherapy drug called Keytruda, which was delivered intravenously once every three weeks. Keytruda had only been approved for about a year at that point.

New drugs such as Keytruda are a type of immunotherapy called checkpoint inhibitors. Most people have a type of protein that stops their immune systems from fighting the cancerous cells. Keytruda and similar drugs block those proteins. It’s like taking down a guard tower, allowing the body’s own immune system force to flood past a barrier, where it then gets to work killing and clearing away the cancer cells.

Checkpoint inhibitors were first approved to treat melanoma but have since gone on to tackle lung cancer, bladder cancer, blood cancers, and other cancers.

Dan Chen, vice president and global head of cancer immunotherapy development at Genentech, told Business Insider that he considers Genentech’s checkpoint inhibitor, Tecentriq, to be the foundation of the company’s cancer immunotherapy program. It’s the first FDA-approved immunotherapy for Genentech, and the company’s already started looking for ways to combine Tecentriq with other cancer immunotherapy drugs that activate the body’s immune system in different ways.

“This is a critical program for us. It allowed us to learn an enormous amount about cancer immunity,” like how the drugs work to inhibit the checkpoints, Chen said.

Genentech points to patients like Bob Schoenbauer to show why the company is “investing more than ever to bring personalised cancer immunotherapy (PCI) to people with cancer.”

Schoenbauer had been diagnosed with late-stage inoperable lung cancer in 2013. Soon after, Schoenbauer was connected with a clinical trial of Tecentriq out of Georgetown University.

“Almost immediately, the cough was going away,” his wife, Frances, told Business Insider. “It worked so fast, I couldn’t believe how good he was feeling.”

Schoenbauer, who still gets Tecentriq every three weeks, is active and walks to the mall in his Maryland town every morning. He’s in remission and says he hasn’t experienced any major side effects from the drug.

But even with this level of excitement, and anecdotal cases like Carter and Schoenbauer, there are some major caveats. First, not everyone is responding to the drugs — for advanced stages of melanoma, the number of people still alive after two years was about 35%, compared to 29.7% over the same time for those taking chemotherapy. And sometimes new checkpoint inhibitors under development fail key trials. In August, Bristol-Myers Squibb, a company with a checkpoint inhibitor called Opdivo said the drug failed a key lung-cancer trial study.

Side effects

Just like chemotherapy and radiation, immunotherapy can have side effects, but they tend to look very different than those from the other treatments. That’s because they originate in the immune system.

Those checkpoint inhibitors act as “checkpoints” for a reason. In a normal body, they keep the immune system from going after healthy cells. So manipulating them, while it might help kill cancer cells, can at times be a blunt instrument. The newly freed immune system can, in some cases, start attacking healthy organs in the body, including the kidneys, liver, adrenal and pituitary glands, and, in some cases, the heart, The New York Times reports.

For example, a person on immunotherapy might experience gastrointestinal problems, such as diarrhoea, that could get more serious and turn into the autoimmune disease colitis.

“We are playing with fire,” UCLA oncologist Dr. John Timmerman told The Times.

Immunotherapy nonprofit Cancer Research Institute CEO Jill O’Donnell-Tormey told Business Insider in October that many of these side effects can be controlled with steroids, but it takes good communication between doctors and patients.

Because it is still so new compared to chemotherapy, understanding and knowing how to treat all these side effects is still a challenge. Researchers are trying to figure out why some people, such as Bob Schoenbauer, don’t seem to have any side effects while others have serious responses, and can the side effects be caught and treated early.

“We follow the science. We try to think through the safety and clinical profiles, and we do think about pros and cons,” Arun Balakumaran, an executive director at Merck told Business Insider regarding how Merck thinks about side effects for Keytruda.

Beyond checkpoints

The field of checkpoint inhibitors has exploded. Take, for instance, Balakumaran at Merck. Two years ago, he said, he was a one-man show at the American Society of Hematology, a major industry conference in December, where data from blood-cancer treatments often debuts. This year, the Merck team had much more data to show, including results from two clinical trials.

Researchers are looking into how those checkpoint inhibitors can be combined, either with chemotherapy or other immunotherapies as well, which could get expensive.

But it’s not the only approach researchers are taking to harness the body’s immune system.

One promising route is CAR T-cell therapy. Short for “chimeric antigen receptor” T-cell therapy, the treatment takes a person’s own cells, takes them out of the body, reengineers them, then puts the cells back in the body where they can attack a particular cancer cell.

There are a couple of companies leading the charge in developing these treatments.

Novartis plans to file for FDA approval in early 2017 for its therapy, called CTL019. At ASH, Novartis presented clinical data that showed that the treatment eliminated acute lymphoblastic leukemia, an aggressive blood cancer, in 82% of the patients treated.

Kite Pharma, a company with a rival therapy to Novartis, also hopes to file with the FDA by the end of the first quarter in 2017.

Bluebird Bio is developing gene and therapies for diseases including multiple myeloma, another form of blood cancer that affects plasma. “Basically we sent a T cell in to attach to the myeloma cells, and then basically blow them up,” Bluebird CEO Nick Leschly told Business Insider.

But anytime you’re “blowing up” cancer cells, there can be some major risks. Juno Therapeutics, another biotech company working on these cell therapies, stopped its leading CAR-T clinical trial after patients died while on the trial.

At the end of November, Bluebird gave results from its six-person phase-one trial in patients with myeloma who hadn’t responded to other treatments. Of the patients who got a higher dose of the gene therapy, 100% saw tumour shrinkage.

Mark Alles, CEO of Celgene, the biotech company that teamed up with Bluebird on this myeloma treatment, called the response from these patients exceptional. At the Forbes Healthcare Summit on December 1, he continued, saying it’s important to keep in mind how small this trial was: “That’s the caveat, always the caveat, let’s be careful not to get ahead of ourselves.”